There are now 50+ new drugs in Phase II-III development to treat COPD - a disease affecting 13 million Americans, costing $49B and killing 120,000 each year. However, a major limitation in evaluating therapies for these chronic diseases is the lack of a sufficiently sensitive and non-invasive method for drug developers to see efficacy on timescales of days rather than months. Without such methods, expensive drug development programs fail, and promising new drugs are never put into trials. An emerging solution is hyperpolarized 129Xe MRI, which is an extraordinarily powerful marker of regional pulmonary function and therapy response. However, its availability in major pulmonary centers is currently limited. Our long-term goal is to build a business that can broadly deploy non-invasive, high-resolution hyperpolarized 129Xe MRIs as a biomarker to help accelerate evaluation of promising therapies for respiratory diseases. The objective of this application is to improve the size, conversion efficiency, and hence the economics of the optical cell within 129Xe polarizers. The critical need is that today's hyperpolarization technology is relatively inefficient in converting laser power into spin-polarized 129Xe. Over 80% of the available laser power is not productively converted into spin polarization. Adding additional laser power and optical cell volume to overcome conversion inefficiency results in large, expensive units that must be installed in a dedicated room, with a source of compressed air, external gas cylinders, and 3-phase power in close proximity to the MRI scanner. The rationale for the proposed project is that by using a novel optical cell geometry, it will become possible to produce highly polarized 129Xe in a small, compact, economical system employing modest laser power and requiring nothing unusual of the facility. By solving this critical bottleneck, we remove major limitations fr clinical trials requiring ~20 sites to be brought on line quickly and temporarily to meet recruitment targets. Thus, the proposed research is relevant to that part of the NIH Mission that pertains to improving health by developing and accelerating the application of biomedical technologies. Guided by strong preliminary data, our design approach relies on two Specific Aims: 1) Develop a standard platform for operating and testing various new optical cell designs, and 2) Develop enhanced optical cell geometry by optimizing photon efficiency. Completion of these aims will: a) deliver a fundamentally new and improved approach to efficient optical pumping in 129Xe polarizers, b) directly measure the key performance characteristics of this new design to maximize polarization levels and throughput, and c) develop the integrated control and monitoring package needed to commercialize such a product. The proposed approach is innovative because it takes a fundamentally new approach to optical cell design that will reduce the size and facility footprint of hyperpolarization technology while improving it performance. The proposed research is significant because realization of such technology will greatly accelerate the deployment of hyperpolarized 129Xe as a biomarker in clinical trials for chronic lung disease therapies.